These deaths made national headlines and spurred considerable speculation as to the viral cause, but in the end we learned that it was seasonal H3N2 influenza, exacerbated by a MRSA (or necrotizing) pneumonia co-infection.

Bacterial pneumonia, secondary to a viral respiratory illness, is an all-too-common, and sometimes deadly complication.

And if you think about it, the conditions produced by flu – excess fluid in the lungs and elevated body temperatures – provide the ideal warm, moist environment where bacteria can thrive.

But scientists have long believed there had to be other, more subtle causes of increased bacterial pneumonia in flu patients.

We’ve research this week that suggests that the body’s innate immune system – part of the body’s generic immune defense – becomes less able to deal with bacteria when combating a viral infection.

But first, a little background is in order.

The human immune system is extremely complex, multifaceted, and far from completely understood. But in the simplest of terms, we have two basic types of immune defense systems:

First, we have natural immunity – so called `innate immunity’ – that can detect, and launch a generic defense against a wide variety of invading pathogens

Were it not for this built-in immunity, none of us would survive past the first few hours or days of life as we'd be quickly overrun by opportunistic infections.

For our innate immunity to work, it must have a way to recognize an infective agent, even one it has never seen before. Toll-like receptors (TLRs) are a type of protein that are able to recognize molecules that are broadly shared by infectious agents called PAMPs (Pathogen-Associated Molecular Patterns).

In other words, PAMPs are an easily recognizable molecular signature that tells our innate immune system that we have been infected . . . with something.

The Innate immune system buys us time for the second part of our immune system - our Adaptive Immune System - to learn to recognize and fight specific pathogens.

Theadaptive immune system produces pathogen-specific antibodies after exposure to a virus that can provide us with varying degrees of acquired immunity.

This acquired immunity explains why we rarely get the same virus twice, and why vaccines work.

All of which serves as background for a study that appeared earlier this week in The Journal of Innate Immunology - led by researchers at the Helmholtz Centre for Infection Research (HZI) - that focused in on Toll-like Receptor 7(TLR7) as possibly promoting bacterial growth during a viral infection.

The entire paper is behind a pay wall, but the abstract may be read at the link above. Luckily we have a press release from HZI describing their findings. Excerpts below, but follow the link to read it in its entirety.

Influenza curbs part of the immune system and abets bacterial infections

15.11.2012

Manfred Rohde/HZIA scavenger cell of the immune system ingests bacteria (shown in green). During an influenza infection, the macrophages’ appetite is curbed.

When infected with influenza, the body becomes an easy target for bacteria. The flu virus alters the host’s immune system and compromises its capacity to effectively fight off bacterial infections. Now, a team of immunologists at the Helmholtz Centre for Infection Research (HZI) and cooperation partners has discovered that an immune system molecule called TLR7 is partly to blame. The molecule recognizes the viral genome – and then signals scavenger cells of the immune system to ingest fewer bacteria. The researchers published their findings in the Journal of Innate Immunity.

<SNIP>

They focused on TLR7, a molecule that is found in different cells of the body. TLR7 is capable of recognizing viral genetic material. As it turns out, TLR7 has an unwanted side effect, too: During a flu infection, it appears to undermine the body’s innate ability to fight off bacteria, thereby increasing the chance of a superinfection.

The researchers made their discovery when they examined how superinfected mice were dealing with the bacterium Streptococcus pneumoniae, the pneumonia pathogen. The scientists colored the bacteria and measured how many of them were taken up by scavenger cells of the immune system called macrophages. The macrophages of TLR7-deficient mice had a bigger appetite and eliminated larger numbers of bacteria when infected with the flu than those of mice with the intact viral sensor. “Without TLR7, it takes longer before influenza-infected mice reach the critical point where they are no longer able to cope with the bacterial infection,” explains Prof. Dunja Bruder, head of HZI’s “Immune Regulation Group” and professor of infection immunology at the University Hospital Magdeburg.

The scientists also have an idea about how TLR7 may be curtailing the scavenger cells’ appetite: Whenever the immune system recognizes a virus, it gets other immune cells to produce a signaling substance called IFN gamma. It is already known that this substance inhibits macrophages in the lungs, causing them to eliminate fewer bacteria. As part of their study, the researchers discovered another indication of this special relationship: In TLR7-deficient animals they found smaller quantities of the IFN gamma messenger substance. The consequence might be that macrophages have a bigger appetite and that therefore bacterial entry into the bloodstream is delayed.

“Our results confirm that in the long run the flu virus suppresses the body’s ability to defend itself against bacteria. Presumably, this is an unwanted side effect of the viral infection,” speculates Dr. Stegemann-Koniszewski, the study’s first author.

In that study scientists at NIAID and the Institute for Systems Biology (ISB) infected experimental mice with both seasonal flu and the 2009 H1N1 pandemic flu, and after 48 hours exposed some of them to Streptococcus pneumoniae, one of the main causes of pneumonia.

Mice that were exposed only to the two flu strains showed expected flu symptoms, but all survived.

Mice that were exposed to seasonal flu andS. pneumoniaeexperienced minor lung damage, but once again, all survived.

But all of the mice infected with the pandemic H1N1 virus, and S. pneumoniae showed severe weight loss, lung damage, and 100% mortality

Indicating that pandemic H1N1, more than seasonal flu, exacerbated an S. pneumoniaeco-infection.

In 2008, we saw a study in The Journal of Infectious Diseases by Morens, Taubenberger, and Fauci that looks at the role of bacterial pneumonia in the high death toll of 1918 (see Viral-Bacterial Copathogenesis).

Less substantial data from the subsequent 1957 and 1968 pandemics are consistent with these findings. If severe pandemic influenza is largely a problem of viral-bacterial copathogenesis, pandemic planning needs to go beyond addressing the viral cause alone (e.g., influenza vaccines and antiviral drugs).

During the 2009 pandemic,I wrote about the CDC Promoting Better Uptake Of PPSV in Adults(Pneumococcal polysaccharide vaccine). While The PPSV vaccine won’t prevent all bacterial pneumonias, it can significantly reduce the number of those who will be affected.

It doesn’t require a pandemic strain to exact a heavy toll, as even in normal flu seasons tens of thousands die from influenza and its complications.

Currently, the PPSV is recommended for those over 65 and those under 65 with specific risk factors for pneumonia (including smokers and those with asthma).

Which is why I heartily recommend everyone talk with their doctor about the advisability of getting the pneumonia vaccine.

For more information on some of the complexities of our immune system, you may wish to revisit some of these earlier blog posts.